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Publication Number
US-11111277-B2
Publication Date
2021-09-07
Expiration Date
Abstract
Provided herein are compositions related to vaccines, e.g., influenza vaccines, including, peptide based vaccines, nucleic acid based vaccines, recombinant virus based vaccines, antibody based vaccines, and virus based vaccines. Also provided herein are methods related to vaccines, e.g., influenza vaccines, including methods of identifying epitopes for the vaccines, producing, formulating, and administering the vaccines.
Core Innovation
The invention relates to influenza vaccine compositions centered on engineered influenza epitope polypeptides. The polypeptides comprise influenza virus epitopes defined by specific, non-naturally occurring amino-acid sequences identified by SEQ ID NOs, and in some embodiments multiple defined epitope components are assembled within a single polypeptide construct.
The disclosed epitope polypeptides include defined sequence identity relationships and specific component epitope sequences. One embodiment recites a polypeptide comprising a set of SEQ ID NOs, while another embodiment recites a polypeptide that includes ten component sequences each having at least 75% sequence identity to corresponding SEQ ID NOs. The constructs may further specify how the component epitope sequences are arranged and connected, including direct linkage and linkage via a linker such as RVKR (SEQ ID NO:110).
The invention further provides optional helper T-cell epitope elements and influenza B NP-derived sequences in engineered epitope polypeptides. Helper T-cell epitopes may include PADRE (SEQ ID NO:101), a PADRE derivative (SEQ ID NO:102), and/or other helper T-cell epitope sequences such as SEQ ID NO:103. The disclosed material also covers related formats including polynucleotides, vectors, recombinant viruses, and virus-like delivery systems, together with broad vaccine formulation and administration route categories.
The document also describes a vaccine and/or pharmaceutical formulation framework for influenza A/B/C that uses immunological targeting concepts and includes antigen presentation approaches involving an Antigen Presenting Cell and dendritic cells. It frames compositions that can include adjuvants and describes virus-based vaccines and engineered virus constructs in which engineered sequences express influenza epitope sequences, including recombinant adenovirus and tandem influenza epitopes separated by a linker sequence.
Claims Coverage
The independent claims cover two distinct polypeptide epitope architectures: one defined by an explicit set of influenza epitope SEQ ID NOs, and one defined by ten component sequences each meeting a minimum sequence identity threshold to corresponding SEQ ID NOs.
Enumerated influenza epitope polypeptide by SEQ ID NO set
A polypeptide comprising influenza virus epitopes, wherein the polypeptide comprises the sequences of SEQ ID NOs: 2, 3, 8, 11, 12, 17, 21, 22, 24, 32, 33, 34, 40, 41, 43, 49, 51, 52, 58, 59, 61, 62, 70, 73, 74, 75, 76, 77, 78, 82, 84, 85, 86, 92, 93, and 94.
Ten-component influenza epitope polypeptide with minimum identity thresholds
A polypeptide comprising influenza virus epitopes, wherein the polypeptide comprises ten sequences each comprising at least 75% sequence identity to corresponding SEQ ID NOs: 8, 11, 12, 2, 3, 32, 24, 17, 29, and 33.
Overall, the independent claims define engineered influenza-virus-epitope polypeptides either by an explicit set of included epitope sequences or by a ten-sequence composition where each component meets a specified minimum sequence identity to a corresponding SEQ ID NO. Dependent claims further cover linkage between component sequences, a specific linker sequence (RVKR, SEQ ID NO:110), translation into a polynucleotide encoding the polypeptide, delivery via a vector, and administration of the resulting composition to a subject.
Stated Advantages
Survival outcomes are reported in examples, including survival after PR8 challenge and survival versus controls in adenovirus epitope constructs.
Immunogenicity assessment is described for a Phase 1 clinical study using IFN-gamma ELISPOT.
Heterosubtypic protection testing is described.
Documented Applications
Influenza vaccination using APC/dendritic-cell-based vaccine concepts.
Influenza vaccination using virus-based vaccines, including live/inactivated engineered virus constructs expressing influenza epitope sequences.
Intranasal immunization with a Pam2Cys-conjugated influenza CD8 peptide, with outcomes assessed after PR8 challenge.
Recombinant adenovirus vaccination expressing tandem influenza epitopes, with reported survival versus controls in a lethal challenge context.
Prime-boost concepts using Pam2Cys prime and recombinant adenovirus/boost as described by the document examples.
Heterosubtypic protection testing design involving an adenovirus vaccine expressing a defined set of tandem influenza B/NP-related epitopes.
A human Phase 1 clinical study for an adenovirus vaccine construct (AdFlu51pep), with immunogenicity assessment by IFN-gamma ELISPOT.
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